SOUTH PLAINFIELD, N.J.—In late November, Roche and PTC
Therapeutics joined forces to tackle
spinal muscular atrophy (SMA), a genetic
neuromuscular disorder that causes muscle weakness. SMA affects one out of
every 10,000 children, but
currently has no effective treatment.

In the hopes of filling this high-unmet medical need, Roche
has licensed PTC's SMA program. The agreement gives PTC $30 million upfront, up
to $460 million in development and commercial milestone payments and
double-digit royalties on commercial sales. Development will be overseen by a
joint steering committee.

At its core, the partnership is "really about developing
first-in-class treatments for a disease with a high, unmet medical need," says
Dr.
Stuart Peltz, president and CEO of PTC. SMA is caused by a missing or
defective SMN1 gene, which results in reduced levels of the survival motor
neuron
(SMN) protein.

Because the disease affects the muscles that control
breathing, SMA can cause
premature death. Life expectancy tends to vary by SMA
type, which is generally associated with age of onset of symptoms. The severity
of symptoms
varies widely depending on SMA type involved and the stage of the
disease, but even its moderate form, SMA can limit function and mobility.
People with
SMA either never acquire, or progressively lose, the ability to
walk, stand, sit and eventually move. People with SMA often develop bone and/or
spinal
deformities that may require surgical treatment. Respiratory illnesses
may be more common for people living with SMA and can be severe.

There is no known cure for the disease, which could be
eligible for orphan status by regulatory authorities. Should
that status be
granted, this could reduce the time needed for a drug to reach patients.

The compounds in PTC's SMA
program treat the underlying
cause of the disorder. Early testing in research models of the disease has
shown that the compounds increase SMN levels in
the central nervous system,
muscles and other tissues. The program includes three compounds currently in
preclinical development, as well as several
potential back-up compounds.

"Not only do we have one compound to move forward, but we
also have
backups, so if for any reason the compounds fail, we have others we
can move forward," notes Peltz.

The basic science of PTC's approach to drug discovery "is
very attractive," says Santarelli, adding that it "unlocks the possibility of
impacting therapeutic targets that would not be possible with standard
approaches."

The
partnership is Roche's first experience working in the
area of SMA, says Luca Santarelli, global head of Roche Neuroscience, and he
adds that the
agreement will boost Roche's work in the area of central nervous
system diseases.

"It is our
goal to get very close to the science and develop
mechanistic agents, allowing us to individualize medicine for every patient.
This makes us different
from a lot of others that have played in this field in
the past, and we believe this goal is part of the reason we are still in this
game," Santarelli
says.

Roche was compelled by "the serious nature of this
condition, its very high unmet need and
the fact that it affects children,"
adds Santarelli. "For me, this was a very strong motivator to identify a
potential treatment. In this case, the
ability to achieve normal-level
expression of a protein lacking because of a genetic deficit is the key to
solving this disease."

Notably, PTC and Roche consider their work a "three-way
partnership," as the SMA Foundation is also closely involved. Founded in 2003,
the
nonprofit organization has to date invested more than $100 million on
developing a portfolio of drug discovery assets to treat SMA. PTC's program has
been developed in partnership with the SMA Foundation, which will remain active
in the collaboration.

"It's quite unique that an advocacy group places patients as
equal members of this kind of collaboration," says Peltz.

The foundation's involvement in the partnership "adds a lot
of value" in that it is scientifically sophisticated, not just dedicated to
providing
funding or other resources for patients.

"Unlike other charitable foundations, this one decided to
go
after the science," Santarelli says. "Their mission is solving the disease and
getting to its root problem. In addition to that, what they bring
to the table
is a connection with the families, caregivers and doctors. This gives us
instant access to a network of patients with whom we conduct
trials and get a
targeted, sophisticated understanding of the disease."

"At the end of the day, these organizations
are not only
your customers, but people who will help or hurt you in moving forward," Peltz
adds. "If they are not yelling for it, there is probably
not someone working on
it. They are not only doing something scientifically exciting, but their
mission is so important. If this works, we will have
changed the lives of these
people."

SUNNYVALE, Calif.—Roche and Labcyte Inc. will cooperate
around high-speed, miniaturized quantitative
PCR (qPCR) to monitor the
expression of tens to thousands of genes for therapeutic research, Roche
announced last month.

According to Roche, this process can be fully automated
using
the Access Workstation from Labcyte, which integrates the Echo liquid
handler with either the LightCycler 480 or LightCycler 1536 Instrument. Gene
expression profiles derived in a one-step process directly from cells can now
be streamlined into a simple automated workflow, significantly increasing
productivity, said Roche.